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Long term methylphenidate exposure and growth in children and adolescents with ADHD. A systematic review and meta-analysis

Long term methylphenidate exposure and growth in children and adolescents with ADHD. A systematic review and meta-analysis
Long term methylphenidate exposure and growth in children and adolescents with ADHD. A systematic review and meta-analysis

BACKGROUND: Methylphenidate (MPH) is an efficacious treatment for ADHD but concerns have been raised about potential adverse effects of extended treatment on growth.

OBJECTIVES: To systematically review the literature, up to December 2018, conducting a meta-analysis of association of long-term (> six months) MPH exposure with height, weight and timing of puberty.

RESULTS: Eighteen studies (ADHD n = 4868) were included in the meta-analysis. MPH was associated with consistent statistically significant pre-post difference for both height (SMD = 0.27, 95% CI 0.16-0.38, p < 0.0001) and weight (SMD = 0.33, 95% CI 0.22-0.44, p < 0.0001) Z scores, with prominent impact on weight during the first 12 months and on height within the first 24-30 months. No significant effects of dose, formulation, age and drug-naïve condition as clinical moderators were found. Data on timing of puberty are currently limited.

CONCLUSIONS: Long-term treatment with MPH can result in reduction in height and weight. However, effect sizes are small with possible minimal clinical impact. Long-term prospective studies may help to clarify the underlying biological drivers and specific mediators and moderators.

Attention deficit/hyperactivity disorder (ADHD), growth, height, methylphenidate, puberty, stimulants, weight
0149-7634
Carucci, Sara
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Balia, Carla
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Gagliano, Antonella
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Lampis, Angelico
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Buitelaar, Jan K
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Danckaerts, Marina
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Dittmann, Ralf W
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Garas, Peter
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Hollis, Chris
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Inglis, Sarah
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Konrad, Kerstin
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Kovshoff, Hanna
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Liddle, Elizabeth B
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McCarthy, Suzanne
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Nagy, Peter
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Panei, Pietro
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Romaniello, Roberta
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Usala, Tatiana
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Wong, Ian C K
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Banaschewski, Tobias
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Sonuga-Barke, Edmund
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Coghill, David
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Zuddas, Alessandro
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Carucci, Sara
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Balia, Carla
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Gagliano, Antonella
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Lampis, Angelico
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Buitelaar, Jan K
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Danckaerts, Marina
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Dittmann, Ralf W
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Garas, Peter
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Hollis, Chris
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Inglis, Sarah
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Konrad, Kerstin
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Kovshoff, Hanna
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Liddle, Elizabeth B
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McCarthy, Suzanne
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Nagy, Peter
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Panei, Pietro
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Romaniello, Roberta
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Usala, Tatiana
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Wong, Ian C K
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Banaschewski, Tobias
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Sonuga-Barke, Edmund
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Coghill, David
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Zuddas, Alessandro
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Carucci, Sara, Balia, Carla, Gagliano, Antonella, Lampis, Angelico, Buitelaar, Jan K, Danckaerts, Marina, Dittmann, Ralf W, Garas, Peter, Hollis, Chris, Inglis, Sarah, Konrad, Kerstin, Kovshoff, Hanna, Liddle, Elizabeth B, McCarthy, Suzanne, Nagy, Peter, Panei, Pietro, Romaniello, Roberta, Usala, Tatiana, Wong, Ian C K, Banaschewski, Tobias, Sonuga-Barke, Edmund, Coghill, David and Zuddas, Alessandro (2020) Long term methylphenidate exposure and growth in children and adolescents with ADHD. A systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews. (doi:10.1016/j.neubiorev.2020.09.031).

Record type: Review

Abstract

BACKGROUND: Methylphenidate (MPH) is an efficacious treatment for ADHD but concerns have been raised about potential adverse effects of extended treatment on growth.

OBJECTIVES: To systematically review the literature, up to December 2018, conducting a meta-analysis of association of long-term (> six months) MPH exposure with height, weight and timing of puberty.

RESULTS: Eighteen studies (ADHD n = 4868) were included in the meta-analysis. MPH was associated with consistent statistically significant pre-post difference for both height (SMD = 0.27, 95% CI 0.16-0.38, p < 0.0001) and weight (SMD = 0.33, 95% CI 0.22-0.44, p < 0.0001) Z scores, with prominent impact on weight during the first 12 months and on height within the first 24-30 months. No significant effects of dose, formulation, age and drug-naïve condition as clinical moderators were found. Data on timing of puberty are currently limited.

CONCLUSIONS: Long-term treatment with MPH can result in reduction in height and weight. However, effect sizes are small with possible minimal clinical impact. Long-term prospective studies may help to clarify the underlying biological drivers and specific mediators and moderators.

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1-s2.0-S0149763420305923-main - Accepted Manuscript
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Accepted/In Press date: 27 September 2020
e-pub ahead of print date: 17 October 2020
Additional Information: Funding Information: Prof. Dittmann has received compensation for serving as consultant or speaker, or he or the institution he works for have received research support or royalties from the organizations or companies indicated: EU (FP7 Programme), US National Institute of Mental Health (NIMH), German Federal Ministry of Health/Regulatory Agency (BMG/BfArM), German Federal Ministry of Education and Research (BMBF), German Research Foundation (DFG), Volkswagen Foundation; Boehringer Ingelheim, Ferring, Janssen-Cilag, Lilly, Lundbeck, Otsuka, Servier, Shire, Sunovion/Takeda and Theravance. He owns Eli Lilly stock. Funding Information: Dr. Elizabeth Liddle has had grant support from the Wellcome Trust. Funding Information: Prof. Sonuga-Barke’s financial declarations are: Speaker fees, and conference support from Shire Pharma. Consultancy from Neurotech solutions, Copenhagen University and Berhanderling, Skolerne, KU Leuven. Book royalties from OUP and Jessica Kingsley. Financial support received from Arrhus Univeristy and Ghent University for visiting Professorships. Grants awarded from MRC, ESRC, Wellcome Trust, European Union, NIHR, Nuffield Foundation, Fonds Wetenschappelijk Onderzoek-Vlaanderen (FWO), MQ – Transforming Mental health, The Waterloo Foundation. Editor-in-Chief JCPP – supported by a buy-out of time to Kings College London and personal Honorarium. Non-financial declarations are: Member of the European ADHD Guidelines Group Funding Information: Prof. Ian Wong reports grants from European Union FP7 programme and Hong Kong Research Gran Council during the conduct of the study; grants from Shire, grants from Janssen-Cilag, grants from Eli-Lily, grants from Pfizer, outside the submitted work; and Prof Wong was a member of the National Institute for Health and Clinical Excellence (NICE) ADHD Guideline Group and the British Association for Psychopharmacology ADHD guideline group and acted as an advisor to Shire. Funding Information: The research leading to these results received support from the European Community’s Seventh Framework Programme ( FP7/2007-2013 ) under grant agreement numbers 260576 (ADDUCE). Publisher Copyright: © 2020
Keywords: Attention deficit/hyperactivity disorder (ADHD), growth, height, methylphenidate, puberty, stimulants, weight

Identifiers

Local EPrints ID: 444975
URI: http://eprints.soton.ac.uk/id/eprint/444975
ISSN: 0149-7634
PURE UUID: e7daa6a3-f346-42cd-8d2d-5a7366d6d1ca
ORCID for Hanna Kovshoff: ORCID iD orcid.org/0000-0001-6041-0376

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Date deposited: 13 Nov 2020 17:33
Last modified: 17 Mar 2024 06:03

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Contributors

Author: Sara Carucci
Author: Carla Balia
Author: Antonella Gagliano
Author: Angelico Lampis
Author: Jan K Buitelaar
Author: Marina Danckaerts
Author: Ralf W Dittmann
Author: Peter Garas
Author: Chris Hollis
Author: Sarah Inglis
Author: Kerstin Konrad
Author: Hanna Kovshoff ORCID iD
Author: Elizabeth B Liddle
Author: Suzanne McCarthy
Author: Peter Nagy
Author: Pietro Panei
Author: Roberta Romaniello
Author: Tatiana Usala
Author: Ian C K Wong
Author: Tobias Banaschewski
Author: Edmund Sonuga-Barke
Author: David Coghill
Author: Alessandro Zuddas

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